bis(2-(tetradecyloxy)ethyl)amine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: bis(2-(tetradecyloxy)ethyl)amine
• 英文别名: 2-tetradecoxy-N-(2-tetradecoxyethyl)ethanamine
• 化学式: C₃₂H₆₇NO₂
• 分子量: 497.889
• InChiKey: DTBAPVZCEJSEEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.8
• 重原子数：
  35
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯乙醇 、 bis(2-(tetradecyloxy)ethyl)amine 在 sodium hydroxide 作用下， 反应 38.0h， 生成 N,N-di[2-n-tetradecyloxyethyl]-N,N-di[2-hydroxyethyl]ammonium chloride
  参考文献：
  名称：

  Anchor Dependency for Non-Glycerol Based Cationic Lipofectins: Mixed Bag of Regular and Anomalous Transfection Profiles

  摘要：

  Although detailed structure activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure - activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1 - 15) of recently reported nonglycerol based monocationic transfection lipids. The C-14 analogues in both series 1 (lipids 1 - 6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C-12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C-10 and C-14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure - activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane reorganizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1 - 15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37degreesC).

  DOI：

  10.1002/1521-3765(20020215)8:4<900::aid-chem900>3.0.co;2-x
• 作为产物：
  描述：

  溴代十四烷 在 咪唑 、 sodium azide 、 四溴化碳 、 水 、 sodium hydride 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.0h， 生成 bis(2-(tetradecyloxy)ethyl)amine
  参考文献：
  名称：

  Anchor Dependency for Non-Glycerol Based Cationic Lipofectins: Mixed Bag of Regular and Anomalous Transfection Profiles

  摘要：

  Although detailed structure activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure - activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1 - 15) of recently reported nonglycerol based monocationic transfection lipids. The C-14 analogues in both series 1 (lipids 1 - 6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C-12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C-10 and C-14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure - activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane reorganizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1 - 15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37degreesC).

  DOI：

  10.1002/1521-3765(20020215)8:4<900::aid-chem900>3.0.co;2-x

文献信息

• LIPID NANO PARTICLES COMPRISING COMBINATION OF CATIONIC LIPID
  申请人：KYOWA HAKKO KIRIN CO., LTD.

  公开号：US20140045913A1

  公开（公告）日：2014-02-13

  The present invention provides a lipid nano-particles, which allow nucleic acids to be easily introduced into cells, comprising a cationic lipid represented by formula (I) (wherein: R 1 and R 2 are, the same or different, alkenyl, etc, and X 3 is absent or is alkyl, etc, X 1 and X 2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and Y 1 is absent or anion, L 1 is a single bond, etc, R 3 is alkyl, etc), and a cationic lipid represented by formula (II) (wherein: R 4 and R 5 are, the same or different, alkenyl, etc, and X 4 and X 5 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X 6 is absent or is alkyl, etc, Y 2 is absent or anion, a and b are, the same or different, 0 to 3, and L 4 is a single bond, etc, R 6 is alkyl, etc, L 2 and L 3 are —O—, —CO—O— or —O—CO—), and the like.

  本发明提供了一种脂质纳米粒子，可以使核酸轻松地进入细胞，包括由式(I)表示的阳离子脂质（其中：R1和R2是相同或不同的烯基等，X3不存在或是烷基等，X1和X2是氢原子，或结合在一起形成单键或亚烷基，Y1不存在或是阴离子，L1是单键等，R3是烷基等），以及由式(II)表示的阳离子脂质（其中：R4和R5是相同或不同的烯基等，X4和X5是氢原子，或结合在一起形成单键或亚烷基，X6不存在或是烷基等，Y2不存在或是阴离子，a和b是相同或不同的0到3，L4是单键等，R6是烷基等，L2和L3是—O—，—CO—O—或—O—CO—）等。
• Synthesis of Secondary Amines with Long Chains Containing Ether Bonds
  作者：Songdong Ding、Haowei Xu、Xiuying Yang、Lianjun Song、Xueyu Wang、Qiuju Li、Lanlan He

  DOI：10.1055/s-0040-1719921

  日期：2022.7

  secondary amines with long chains containing ether bonds were synthesized by a three-step protection–etherification–deprotection process from diethanolamine. The optimum reaction conditions were examined. This method has the advantages of simplicity, low cost, and high yield. Furthermore, some new downstream products (diglycolamides) were prepared from the ether-containing long-chain secondary amines as reactants

  通过二乙醇胺的三步保护-醚化-去保护过程合成了一类新型的含有醚键的长链仲胺。考察了最佳反应条件。该方法具有简单、成本低、收率高等优点。此外，以含醚的长链仲胺为反应物，制备了一些新的下游产品（二甘醇酰胺），并评估了它们在萃取几种金属离子中的负载能力。
• NUCLEIC ACID-CONTAINING LIPID NANOPARTICLES
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP3275448A1

  公开（公告）日：2018-01-31

  The present invention provides nucleic acid-containing lipid nanoparticles containing a lipid (lipid A) which has a hydrophilic unit having a single quaternary ammonium group, and three independent, optionally substituted hydrocarbon groups, a lipid derivative or fatty acid derivative of a water-soluble polymer, and a nucleic acid.

  本发明提供了含核酸的脂质纳米颗粒，其中含有一种脂质（脂质 A），该脂质具有一个亲水单元，该亲水单元具有一个季铵基团和三个独立的任选取代的烃基、一种水溶性聚合物的脂质衍生物或脂肪酸衍生物以及一种核酸。
• PRODUCTION OF A COMPOSITION CONTAINING A COMPLEX BETWEEN A MEMBRANE COMPOSED OF A LIPID MONOLAYER AND A NUCLEIC ACID, AND, A LIPID MEMBRANE FOR ENCAPSULATING THE COMPLEX THEREIN
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP3301086A1

  公开（公告）日：2018-04-04

  The present invention relates to a method for producing a composition containing a complex between a membrane composed of a lipid monolayer (reversed micelle) and a nucleic acid, and a lipid membrane for encapsulating the complex therein, comprising the following steps A to D: Step A: preparing a complex between the nucleic acid and a liposome comprising a cationic lipid represented by the formula (I) and/or a cationic lipid other than cationic lipid represented by the formula (I); Step B: preparing a dispersion liquid by dispersing the complex in water or ethanol aqueous solution; Step C: preparing a solution by dissolving the formula (I) and/or the cationic lipid other than cationic lipid represented by the formula (I) in ethanol or an ethanol aqueous solution; and Step D: mixing the dispersion liquid and the solution, and optionally adding water; wherein the formula (I) is (wherein: R1 and R2 are, the same or different, each linear or branched alkyl, alkenyl or alkynyl having 12 to 24 carbon atoms, X1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, X3 is absent or is alkyl having 1 to 6 carbon atoms, or alkenyl having 3 to 6 carbon atoms, when X3 is absent, Y is absent, a and b are 0, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, and L1 and L2 are -O-, Y is absent, a and b are, the same or different, 0 to 3, and are not 0 at the same time, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-, Y is absent, a and b are, the same or different, 0 to 3, L3 is a single bond, R3 is a hydrogen atom, and L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-, or Y is absent, a and b are, the same or different, 0 to 3, L3 is -CO- or -CO-O-, R3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, wherein at least one of the substituents is amino, monoalkylamino, dialkylamino, or trialkylammonio, and L1 and L2 are , the same or different, -O-, -CO-O- or -O-CO-, and when X3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms, Y is a pharmaceutically acceptable anion, a and b are, the same or different, 0 to 3, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-).

  本发明涉及一种生产含有由脂质单层（反向胶束）组成的膜与核酸之间的复合物的组合物以及用于将复合物包封在其中的脂质膜的方法，包括以下步骤A至D： 步骤 A：制备核酸与由式（I）代表的阳离子脂质和/或除式（I）代表的阳离子脂质以外的阳离子脂质组成的脂质体之间的复合物； 步骤 B：将复合物分散于水或乙醇水溶液中，制备分散液； 步骤 C：将式（I）和/或式（I）代表的阳离子脂质以外的阳离子脂质溶解在乙醇或乙醇水溶液中，制备溶液；以及 步骤 D：混合分散液和溶液，可选择加水； 其中式 (I) 为 (其中 R1 和 R2 相同或不同，各自为具有 12 至 24 个碳原子的直链或支链烷基、烯基或炔基、 X1 和 X2 为氢原子，或结合在一起形成单键或亚烷基、 X3 不存在或为具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基、 当 X3 不存在时 Y 不存在，a 和 b 为 0，L3 为单键，R3 为具有 1 至 6 个碳原子的烷基、具有 3 至 6 个碳原子的烯基、或具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基，这些取代基相同或不同，为氨基、单烷基氨基、二烷基氨基、三烷基氨基、羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，且 L1 和 L2 为 -O-、 Y 不存在，a 和 b 相同或不同，为 0 至 3，且同时不为 0，L3 为单键，R3 为具有 1 至 6 个碳原子的烷基、具有 3 至 6 个碳原子的烯基，或具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基被 1 至 3 个取代基取代、L1和L2是相同或不同的氨基、单烷基氨基、二烷基氨基、三烷基氨基、羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，-O-、-CO-O-或-O-CO-、 Y 不存在，a 和 b 是相同或不同的 0 至 3，L3 是单键，R3 是氢原子，L1 和 L2 是相同或不同的 -O-、-CO-O- 或 -O-CO-，或 羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，其中至少一个取代基是氨基、单烷基氨基、二烷基氨基或三烷基氨基，且 L1 和 L2 是相同或不同的 -O-、-CO-O- 或 -O-CO-，以及 当 X3 是具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基时，Y 是药学上可接受的阴离子，a 和 b 是相同或不同的 0 至 3，L3 是单键，R3 是具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基，L1 和 L2 是相同或不同的-O-、-CO-O-或-O-CO-）。
• CATIONIC LIPID
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP2567951B1

  公开（公告）日：2018-09-19